chr15-45676215-G-A

Position:

• chr15-45676215-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021199.4(SQOR):​c.769G>A​(p.Val257Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: SQOR NM_021199.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02

Genes affected

SQOR (HGNC:20390): (sulfide quinone oxidoreductase) The protein encoded by this gene may function in mitochondria to catalyze the conversion of sulfide to persulfides, thereby decreasing toxic concencrations of sulfide. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16106254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SQOR	NM_021199.4	c.769G>A	p.Val257Ile	missense_variant	6/10	ENST00000260324.12
SQOR	NM_001271213.2	c.769G>A	p.Val257Ile	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SQOR	ENST00000260324.12	c.769G>A	p.Val257Ile	missense_variant	6/10	1	NM_021199.4	P1
SQOR	ENST00000568606.5	c.769G>A	p.Val257Ile	missense_variant	7/11	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461874 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2023

The c.769G>A (p.V257I) alteration is located in exon 6 (coding exon 5) of the SQRDL gene. This alteration results from a G to A substitution at nucleotide position 769, causing the valine (V) at amino acid position 257 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.0035
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;.;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.40	N;N;N
REVEL	Benign	0.067
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.0010	.;B;B
Vest4		0.059
MutPred		0.42		Gain of ubiquitination at K260 (P = 0.0822);Gain of ubiquitination at K260 (P = 0.0822);Gain of ubiquitination at K260 (P = 0.0822);
MVP		0.18
MPC		0.056
ClinPred		0.58	D
GERP RS		3.9
Varity_R		0.13
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45968413;